1. Field of the Invention
The present invention provides methods and compositions for modulating the expression of Sos1, and antisense and ribozyme compounds specifically hybridizable with Sos1.
2. Description of the Related Art
The deregulation of receptor tyrosine kinases (RTKs) or intracellular tyrosine kinases coupled to Ras activation has been involved in the development of a number of tumors, such as breast, ovarian cancer and leukemia (Pandey et al., Cancer Res. 55:4000-03, 1995; Gishizky, M., Annu. Rep. Med. Chem. 30:247-53, 1995).
Activated RTKs recruit the adaptor protein Grb2 and the guanine nucleotide exchange factor Sos1 to the plasma membrane. Here, Sos1 stimulates the nucleotide exchange on Ras GDP to Ras GTP which leads to a conformational change and activation of Ras. Ras GTP activates several known downstream signaling pathways.
As Sos1 plays a crucial role in the coupling of RTKs and also intracellular tyrosine kinases to Ras activation, there is a need in the art for methods and compositions capable of inhibiting Sos1 activity.